Renin-angiotensin system polymorphisms in relation to hypertension status and obesity in a Tunisian population

Renin-angiotensin system polymorphisms in relation to hypertension status and obesity in a Tunisian population
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DOI:
10.1007/s11033-011-1187-2
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发表时间:
2012-04-01
影响因子:
2.8
通讯作者:
Hammami, Mohamed
Hammami, Mohamed
中科院分区:
生物学4区
文献类型:
--
作者:
Mehri, Sounira;Mahjoub, Sinda;Hammami, Mohamed

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原发性高血压(HTA)是在正常情况下维持心血管内环境平衡的遗传、生理和生化系统之间相互作用紊乱的临床表现。我们研究了血管紧张素原M235T、血管紧张素转换酶插入/缺失(ACE I/D)和血管紧张素II受体1(AT1R)A1166C基因多态性对HTA风险的影响,并评价这些基因多态性与肥胖的关系。采用聚合酶链式反应-限制性片段长度多态性方法和聚合酶链式反应分别对142例高血压病患者和191例正常对照进行AGT、ACE和AGTR基因分型。这三个基因多态与HTA显著相关。携带AT1R基因AGT、ACE和CC基因突变TT的个体患HTA的风险分别增加1.67(P=0.032)、3.09(P<0.001)和3.45(P<0.001)。在调整性别、吸烟、糖尿病、血脂异常、体重指数、甘油三酯、DD、TT和CC等因素后,体重指数是高脂血症的独立危险因素(OR=3.14P<0.001)。体重指数与血管紧张素转换酶基因多态性相关(P=0.035),而与血管紧张素转换酶和血管紧张素Ⅱ受体基因多态性无关。在超重和肥胖组中,高血压患者的比例高达21.8%和13.4%。本研究提示,RAS基因变异体的基因分型未来可能成为HTA临床风险识别的重要组成部分。
Essential hypertension (HTA) is the clinical expression of a disordered interaction between the genetic, physiological, and biochemical systems that under usual conditions maintain cardiovascular homeostasis. We studied the effects of the angiotensinogen M235T, angiotensin converting enzyme insertion/deletion (ACE I/D), and angiotensin II receptor 1 (AT1R) A1166C gene polymorphisms on the risk of HTA and to evaluate the relationship between these polymorphisms and obesity. We performed AGT, ACE and AGTR genotyping in 142 hypertensive patients and 191 control subjects using PCR-RFLP methods and PCR, respectively. The three polymorphisms were significantly associated with HTA. Individuals carrying the mutated TT of AGT, DD of ACE and CC of AT1R genotypes had an 1.67 (P = 0.032), 3.09 (P < 0.001) and 3.45 (P < 0.001)-fold increased risk of HTA. After adjustment for sex, smoking, diabetes, dyslipidemia, BMI, triglycerides and DD, TT and CC genotypes, BMI was independent risk factor of HTA (OR = 3.14; P < 0.001). An association of BMI with ACE gene polymorphism (P = 0.035), whereas no association with AGT and AT1R gene polymorphisms was obtained. The proportion of hypertensives is as high as 21.8 and 13.4% in the overweight and the obese DD group. The present study implies that the genotyping for the variants of RAS gene could in the future become an important part of the clinical process of risk identification for HTA.